Mechanisms of disease: The hygiene hypothesis revisited

Francisco Guarner, Raphaëlle Bourdet-Sicard, Per Brandtzaeg, Harsharnjit S. Gill, Peter McGuirk, Willem van Eden, James Versalovic, Joel V. Weinstock, Graham A.W. Rook

Research output: Contribution to journalReview articlepeer-review

239 Scopus citations


In industrialized countries the incidence of diseases caused by immune dysregulation has risen. Epidemiologic studies initially suggested this was connected to a reduction in the incidence of infectious diseases; however, an association with defects in immunoregulation is now being recognized. Effector TH1 and TH2 cells are controlled by specialized subsets of regulatory T cells. Some pathogens can induce regulatory cells to evade immune elimination, but regulatory pathways are homeostatic and mainly triggered by harmless microorganisms. Helminths, saprophytic mycobacteria, bifidobacteria and lactobacilli, which induce immunoregulatory mechanisms in the host, ameliorate aberrant immune responses in the setting of allergy and inflammatory bowel disease. These organisms cause little, if any, harm, and have been part of human microecology for millennia; however, they are now less frequent or even absent in the human environment of westernized societies. Deficient exposure to these 'old friends' might explain the increase in immunodysregulatory disorders. The use of probiotics, prebiotics, helminths or microbe-derived immunoregulatory vaccines might, therefore, become a valuable approach to disease.

Original languageEnglish (US)
Pages (from-to)275-284
Number of pages10
JournalNature Clinical Practice Gastroenterology and Hepatology
Issue number5
StatePublished - May 2006


  • Microbiota
  • Prebiotics
  • Probiotics
  • Regulatory T cells
  • Tolerance

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology


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